ES2326264T3 - Combinacion que comprende un inhibidor de transduccion de señal y un derivado epotilona. - Google Patents

Combinacion que comprende un inhibidor de transduccion de señal y un derivado epotilona. Download PDF

Info

Publication number: ES2326264T3
Authority: ES; Spain
Prior art keywords: hydrogen; lower alkyl; formula; combination; pharmaceutically acceptable
Prior art date: 2001-02-27
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES02744903T

Other languages

English (en)

Spanish (es)

Inventor

Elisabeth Buchdunger

Carl-Henrik Heldin

Arne Ostman

Kristian Pietras

Terence O'reilly

John David Rothermel

Peter Traxler

Markus Wartmann

Ralf Brandt

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Novartis AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-02-27

Filing date

2002-02-26

Publication date

2009-10-06

2001-02-27 Priority claimed from GBGB0104840.4A external-priority patent/GB0104840D0/en

2002-02-26 Application filed by Novartis AG filed Critical Novartis AG

2009-10-06 Application granted granted Critical

2009-10-06 Publication of ES2326264T3 publication Critical patent/ES2326264T3/es

2022-02-26 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000003112 inhibitor Substances 0.000 title claims description 19
230000019491 signal transduction Effects 0.000 title claims description 5
238000011282 treatment Methods 0.000 claims abstract description 27
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
125000000217 alkyl group Chemical group 0.000 claims description 57
229910052739 hydrogen Inorganic materials 0.000 claims description 49
239000001257 hydrogen Substances 0.000 claims description 49
-1 4-pyrazinyl Chemical group 0.000 claims description 34
230000000694 effects Effects 0.000 claims description 31
206010028980 Neoplasm Diseases 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 30
150000001875 compounds Chemical class 0.000 claims description 28
239000004480 active ingredient Substances 0.000 claims description 27
150000003883 epothilone derivatives Chemical class 0.000 claims description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
201000010099 disease Diseases 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 17
230000002062 proliferating effect Effects 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 16
150000002431 hydrogen Chemical class 0.000 claims description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
229940126062 Compound A Drugs 0.000 claims description 11
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 11
108091008606 PDGF receptors Proteins 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
239000003937 drug carrier Substances 0.000 claims description 11
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 claims description 11
102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 claims description 10
229940079593 drug Drugs 0.000 claims description 10
XRYJULCDUUATMC-CYBMUJFWSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 XRYJULCDUUATMC-CYBMUJFWSA-N 0.000 claims description 9
150000001721 carbon Chemical group 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
108010055723 PDGF receptor tyrosine kinase Proteins 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 6
239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 6
150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 4
125000004103 aminoalkyl group Chemical group 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
125000004428 fluoroalkoxy group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical group 0.000 claims description 3
125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
238000000034 method Methods 0.000 abstract description 12
QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 29
HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 26
QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 25
229960002411 imatinib Drugs 0.000 description 22
YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 22
239000002253 acid Substances 0.000 description 16
241001465754 Metazoa Species 0.000 description 10
241000699670 Mus sp. Species 0.000 description 8
102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 8
108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 8
238000012360 testing method Methods 0.000 description 8
239000000203 mixture Substances 0.000 description 7
102400001368 Epidermal growth factor Human genes 0.000 description 6
101800003838 Epidermal growth factor Proteins 0.000 description 6
230000009286 beneficial effect Effects 0.000 description 6
229940116977 epidermal growth factor Drugs 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000002552 dosage form Substances 0.000 description 5
125000004356 hydroxy functional group Chemical group O* 0.000 description 5
239000004615 ingredient Substances 0.000 description 5
125000004043 oxo group Chemical group O=* 0.000 description 5
229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229930013356 epothilone Natural products 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
208000032612 Glial tumor Diseases 0.000 description 3
206010018338 Glioma Diseases 0.000 description 3
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
239000005411 L01XE02 - Gefitinib Substances 0.000 description 3
208000024770 Thyroid neoplasm Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000000996 additive effect Effects 0.000 description 3
230000001142 anti-diarrhea Effects 0.000 description 3
229940125714 antidiarrheal agent Drugs 0.000 description 3
239000003793 antidiarrheal agent Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
230000012010 growth Effects 0.000 description 3
229940084651 iressa Drugs 0.000 description 3
239000000047 product Substances 0.000 description 3
108091008598 receptor tyrosine kinases Proteins 0.000 description 3
102000027426 receptor tyrosine kinases Human genes 0.000 description 3
230000009467 reduction Effects 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000003826 tablet Substances 0.000 description 3
201000002510 thyroid cancer Diseases 0.000 description 3
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
230000003442 weekly effect Effects 0.000 description 3
DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 2
RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010012735 Diarrhoea Diseases 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
108010016076 Octreotide Proteins 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
206010060862 Prostate cancer Diseases 0.000 description 2
208000000236 Prostatic Neoplasms Diseases 0.000 description 2
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
239000000654 additive Substances 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
150000003863 ammonium salts Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 2
229960001433 erlotinib Drugs 0.000 description 2
AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
150000003951 lactams Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
238000004806 packaging method and process Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
238000009097 single-agent therapy Methods 0.000 description 2
239000012453 solvate Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000026683 transduction Effects 0.000 description 2
238000010361 transduction Methods 0.000 description 2
230000009466 transformation Effects 0.000 description 2
230000004614 tumor growth Effects 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 1
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
LVRVABPNVHYXRT-BQWXUCBYSA-N 52906-92-0 Chemical compound C([C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)C1=CC=CC=C1 LVRVABPNVHYXRT-BQWXUCBYSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
XCJHPJRSYNUWET-UHFFFAOYSA-N C(C)(=O)OC1=C(C(=O)O)C=CC=C1.O(C1=CC=CC=C1)C1=C(C(=O)O)C=CC=C1 Chemical compound C(C)(=O)OC1=C(C(=O)O)C=CC=C1.O(C1=CC=CC=C1)C1=C(C(=O)O)C=CC=C1 XCJHPJRSYNUWET-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
102000001301 EGF receptor Human genes 0.000 description 1
108060006698 EGF receptor Proteins 0.000 description 1
BEFZAMRWPCMWFJ-JRBBLYSQSA-N Epothilone C Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C=C\C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C BEFZAMRWPCMWFJ-JRBBLYSQSA-N 0.000 description 1
XOZIUKBZLSUILX-SDMHVBBESA-N Epothilone D Natural products O=C1[C@H](C)[C@@H](O)[C@@H](C)CCC/C(/C)=C/C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C XOZIUKBZLSUILX-SDMHVBBESA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
206010027540 Microcytosis Diseases 0.000 description 1
102000029749 Microtubule Human genes 0.000 description 1
108091022875 Microtubule Proteins 0.000 description 1
102400001357 Motilin Human genes 0.000 description 1
101800002372 Motilin Proteins 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
208000003788 Neoplasm Micrometastasis Diseases 0.000 description 1
239000008896 Opium Substances 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
229930012538 Paclitaxel Natural products 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
102000001253 Protein Kinase Human genes 0.000 description 1
102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
241000700159 Rattus Species 0.000 description 1
101100496572 Rattus norvegicus C6 gene Proteins 0.000 description 1
108091005682 Receptor kinases Proteins 0.000 description 1
238000011579 SCID mouse model Methods 0.000 description 1
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
239000004473 Threonine Substances 0.000 description 1
208000033781 Thyroid carcinoma Diseases 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
208000037844 advanced solid tumor Diseases 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Chemical class 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000005277 alkyl imino group Chemical group 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000006383 alkylpyridyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229960004909 aminosalicylic acid Drugs 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000001028 anti-proliverative effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
229940093265 berberine Drugs 0.000 description 1
QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
ZREIPSZUJIFJNP-UHFFFAOYSA-K bismuth subsalicylate Chemical compound C1=CC=C2O[Bi](O)OC(=O)C2=C1 ZREIPSZUJIFJNP-UHFFFAOYSA-K 0.000 description 1
229960000782 bismuth subsalicylate Drugs 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
229950002826 canertinib Drugs 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
229960005395 cetuximab Drugs 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
229960004126 codeine Drugs 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
238000011284 combination treatment Methods 0.000 description 1
239000013065 commercial product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
238000013461 design Methods 0.000 description 1
BEFZAMRWPCMWFJ-UHFFFAOYSA-N desoxyepothilone A Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC=CCC1C(C)=CC1=CSC(C)=N1 BEFZAMRWPCMWFJ-UHFFFAOYSA-N 0.000 description 1
XOZIUKBZLSUILX-UHFFFAOYSA-N desoxyepothilone B Natural products O1C(=O)CC(O)C(C)(C)C(=O)C(C)C(O)C(C)CCCC(C)=CCC1C(C)=CC1=CSC(C)=N1 XOZIUKBZLSUILX-UHFFFAOYSA-N 0.000 description 1
238000011161 development Methods 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229960004192 diphenoxylate Drugs 0.000 description 1
HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
BEFZAMRWPCMWFJ-QJKGZULSSA-N epothilone C Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 BEFZAMRWPCMWFJ-QJKGZULSSA-N 0.000 description 1
XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
208000014829 head and neck neoplasm Diseases 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000003908 liver function Effects 0.000 description 1
RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
229960001571 loperamide Drugs 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
238000012792 lyophilization process Methods 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
229950008001 matuzumab Drugs 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
210000004688 microtubule Anatomy 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000000472 muscarinic agonist Substances 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
150000002829 nitrogen Chemical group 0.000 description 1
208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229960002700 octreotide Drugs 0.000 description 1
239000003921 oil Substances 0.000 description 1
229940005483 opioid analgesics Drugs 0.000 description 1
229960001027 opium Drugs 0.000 description 1
229940026778 other chemotherapeutics in atc Drugs 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
229960001592 paclitaxel Drugs 0.000 description 1
229960001972 panitumumab Drugs 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000001814 pectin Substances 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
201000002025 prostate sarcoma Diseases 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
230000009822 protein phosphorylation Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
229940072272 sandostatin Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000005507 spraying Methods 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000007940 sugar coated tablet Substances 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
208000013077 thyroid gland carcinoma Diseases 0.000 description 1
229940098465 tincture Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
201000005112 urinary bladder cancer Diseases 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Cosmetics (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

ES02744903T 2001-02-27 2002-02-26 Combinacion que comprende un inhibidor de transduccion de señal y un derivado epotilona. Expired - Lifetime ES2326264T3 (es)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GBGB0104840.4A GB0104840D0 (en)	2001-02-27	2001-02-27	Use of organic compounds
GB0104840		2001-02-27
US33904001P	2001-10-30	2001-10-30
US339040P		2001-10-30

Publications (1)

Publication Number	Publication Date
ES2326264T3 true ES2326264T3 (es)	2009-10-06

Family

ID=26245767

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES02744903T Expired - Lifetime ES2326264T3 (es)	2001-02-27	2002-02-26	Combinacion que comprende un inhibidor de transduccion de señal y un derivado epotilona.

Country Status (22)

Country	Link
US (1)	US7723339B2 (pl)
EP (1)	EP1385522B1 (pl)
JP (1)	JP4499359B2 (pl)
KR (1)	KR100848197B1 (pl)
CN (1)	CN1511036B (pl)
AT (1)	ATE434438T1 (pl)
AU (1)	AU2002308218B2 (pl)
BR (1)	BR0207649A (pl)
CA (1)	CA2439268C (pl)
CY (1)	CY1109347T1 (pl)
DE (1)	DE60232719D1 (pl)
DK (1)	DK1385522T3 (pl)
ES (1)	ES2326264T3 (pl)
IL (2)	IL157466A0 (pl)
MX (1)	MXPA03007729A (pl)
NO (1)	NO325416B1 (pl)
NZ (1)	NZ527764A (pl)
PL (1)	PL207197B1 (pl)
PT (1)	PT1385522E (pl)
RU (1)	RU2313345C2 (pl)
SK (1)	SK287489B6 (pl)
WO (1)	WO2002067941A2 (pl)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1386922B1 (en)	1996-12-03	2012-04-11	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereof, analogues and uses thereof
US6204388B1 (en)	1996-12-03	2001-03-20	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
ATE554756T1 (de)	2001-03-14	2012-05-15	Bristol Myers Squibb Co	Kombination aus epothilon-analog und chemotherapeutika zur behandlung von proliferativen erkrankungen
AU2002342335B2 (en) *	2001-05-16	2006-02-02	Novartis Ag	Combination comprising N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2pyrimidine-amine and a chemotherapeutic agent
EP1704863A3 (en) *	2001-05-16	2010-11-24	Novartis AG	Combination comprising N-5-4-(4-Methyl-Piperazino-Methyl-)Benzoyla Mido]-2-Methylphenyl -4-(3-Pyridyl)-2Phyrimidine-amine and a chemotherapeutic agent
US20050038048A1 (en) *	2001-10-29	2005-02-17	Ball Howard Ashley	Use of 7h-pyrrollo{2,3-d}pyrimidine derivatives in the treatment of solid tumor diseases
ATE350383T1 (de)	2002-08-23	2007-01-15	Sloan Kettering Inst Cancer	Synthese von epothilonen, zwischenprodukte dafür, analoga und deren verwendungen
US6921769B2 (en)	2002-08-23	2005-07-26	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
US7649006B2 (en)	2002-08-23	2010-01-19	Sloan-Kettering Institute For Cancer Research	Synthesis of epothilones, intermediates thereto and analogues thereof
US20050171167A1 (en) *	2003-11-04	2005-08-04	Haby Thomas A.	Process and formulation containing epothilones and analogs thereof
US20060121511A1 (en)	2004-11-30	2006-06-08	Hyerim Lee	Biomarkers and methods for determining sensitivity to microtubule-stabilizing agents
JO2596B1 (en) *	2004-11-30	2011-02-27	نوفارتيس ايه جي	Compositions include epothelones and tyrosine protein kinase inhibitors and their pharmaceutical uses
EP2634252B1 (en)	2005-02-11	2018-12-19	University of Southern California	Method of expressing proteins with disulfide bridges
US8008256B2 (en) *	2006-05-01	2011-08-30	University Of Southern California	Combination therapy for treatment of cancer
US8802394B2 (en)	2008-11-13	2014-08-12	Radu O. Minea	Method of expressing proteins with disulfide bridges with enhanced yields and activity
WO2010108503A1 (en)	2009-03-24	2010-09-30	Life & Brain Gmbh	Promotion of neuronal integration in neural stem cell grafts
CA2927832C (en)	2010-05-18	2021-03-23	Cerulean Pharma Inc.	Cyclodextrin-containing polymer-therapeutic agent conjugates and their use

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1989006692A1 (en) *	1988-01-12	1989-07-27	Genentech, Inc.	Method of treating tumor cells by inhibiting growth factor receptor function
DE4138042C2 (de)	1991-11-19	1993-10-14	Biotechnolog Forschung Gmbh	Epothilone, deren Herstellungsverfahren sowie diese Verbindungen enthaltende Mittel
TW225528B (pl) *	1992-04-03	1994-06-21	Ciba Geigy Ag
US5654307A (en) *	1994-01-25	1997-08-05	Warner-Lambert Company	Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family
PL188959B1 (pl) *	1995-07-06	2005-05-31	Novartis Ag	Pirolopirymidyny i sposoby ich wytwarzania
ATE267197T1 (de)	1996-11-18	2004-06-15	Biotechnolog Forschung Gmbh	Epothilon d, dessen herstellung und dessen verwendung als cytostatisches mittel bzw. als pflanzenschutzmittel
CO4940418A1 (es) *	1997-07-18	2000-07-24	Novartis Ag	Modificacion de cristal de un derivado de n-fenil-2- pirimidinamina, procesos para su fabricacion y su uso
US6302838B1 (en) *	1998-02-25	2001-10-16	Novartis Ag	Cancer treatment with epothilones
AU5036999A (en) *	1998-06-30	2000-01-17	Schering Aktiengesellschaft	Epothilon derivatives, their preparation process, intermediate products and their pharmaceutical use
EE200100422A (et) *	1999-02-11	2002-12-16	Schering Aktiengesellschaft	Epotilooni derivaadid, nende valmistamismeetod jafarmatseutiline kasutamine
DE19908760A1 (de) *	1999-02-18	2000-08-24	Schering Ag	Neue Epothilon-Derivate, Verfahren zu deren Herstellung und ihre pharmazeutische Verwendung

2002
- 2002-02-26 PL PL363288A patent/PL207197B1/pl not_active IP Right Cessation
- 2002-02-26 PT PT02744903T patent/PT1385522E/pt unknown
- 2002-02-26 NZ NZ527764A patent/NZ527764A/en not_active IP Right Cessation
- 2002-02-26 AT AT02744903T patent/ATE434438T1/de active
- 2002-02-26 JP JP2002567308A patent/JP4499359B2/ja not_active Expired - Fee Related
- 2002-02-26 ES ES02744903T patent/ES2326264T3/es not_active Expired - Lifetime
- 2002-02-26 SK SK1071-2003A patent/SK287489B6/sk not_active IP Right Cessation
- 2002-02-26 CA CA002439268A patent/CA2439268C/en not_active Expired - Fee Related
- 2002-02-26 KR KR1020037011205A patent/KR100848197B1/ko not_active Expired - Fee Related
- 2002-02-26 WO PCT/EP2002/002049 patent/WO2002067941A2/en not_active Ceased
- 2002-02-26 CN CN028056086A patent/CN1511036B/zh not_active Expired - Fee Related
- 2002-02-26 EP EP02744903A patent/EP1385522B1/en not_active Expired - Lifetime
- 2002-02-26 DK DK02744903T patent/DK1385522T3/da active
- 2002-02-26 RU RU2003127392/15A patent/RU2313345C2/ru not_active IP Right Cessation
- 2002-02-26 DE DE60232719T patent/DE60232719D1/de not_active Expired - Lifetime
- 2002-02-26 IL IL15746602A patent/IL157466A0/xx unknown
- 2002-02-26 MX MXPA03007729A patent/MXPA03007729A/es active IP Right Grant
- 2002-02-26 AU AU2002308218A patent/AU2002308218B2/en not_active Ceased
- 2002-02-26 US US10/469,367 patent/US7723339B2/en not_active Expired - Fee Related
- 2002-02-26 BR BR0207649-7A patent/BR0207649A/pt not_active Application Discontinuation
2003
- 2003-08-18 IL IL157466A patent/IL157466A/en not_active IP Right Cessation
- 2003-08-25 NO NO20033769A patent/NO325416B1/no not_active IP Right Cessation
2009
- 2009-08-28 CY CY20091100900T patent/CY1109347T1/el unknown

Also Published As

Publication number	Publication date
RU2003127392A (ru)	2005-03-27
US20040132754A1 (en)	2004-07-08
NZ527764A (en)	2006-01-27
PT1385522E (pt)	2009-09-04
DK1385522T3 (da)	2009-10-12
DE60232719D1 (de)	2009-08-06
ATE434438T1 (de)	2009-07-15
HK1062266A1 (en)	2004-10-29
BR0207649A (pt)	2004-03-09
JP2004527493A (ja)	2004-09-09
SK10712003A3 (sk)	2004-02-03
EP1385522B1 (en)	2009-06-24
WO2002067941A2 (en)	2002-09-06
WO2002067941A3 (en)	2003-11-20
JP4499359B2 (ja)	2010-07-07
NO20033769D0 (no)	2003-08-25
US7723339B2 (en)	2010-05-25
SK287489B6 (sk)	2010-11-08
PL363288A1 (pl)	2004-11-15
PL207197B1 (pl)	2010-11-30
KR100848197B1 (ko)	2008-07-24
CN1511036B (zh)	2010-05-05
KR20040025900A (ko)	2004-03-26
WO2002067941A8 (en)	2003-12-18
NO20033769L (no)	2003-08-25
IL157466A0 (en)	2004-03-28
IL157466A (en)	2012-04-30
EP1385522A2 (en)	2004-02-04
AU2002308218B2 (en)	2005-11-10
CA2439268A1 (en)	2002-09-06
NO325416B1 (no)	2008-04-21
RU2313345C2 (ru)	2007-12-27
CN1511036A (zh)	2004-07-07
CA2439268C (en)	2010-01-19
MXPA03007729A (es)	2003-12-04
CY1109347T1 (el)	2014-07-02

Publication	Publication Date	Title
EP1385522B1 (en)	2009-06-24	Combination comprising a signal transduction inhibitor and an epothilone derivative
KR101292508B1 (ko)	2013-08-01	백혈병의 치료를 위한, 피리미딜아미노벤즈아미드 화합물과 조합된 ｃ-ｓｒｃ 억제제의 용도
AU2002308218A1 (en)	2003-03-06	Combination comprising a signal transduction inhibitor and an epothilone derivative
US20110281902A1 (en)	2011-11-17	Combinations comprising a protein kinase inhibitor being a pyrimidylaminobenzamide compound and a hsp90 inhibitor such as 17-aag
US20120053559A1 (en)	2012-03-01	Treatment of Proliferative Diseases with Epothilone Derivatives and Radiation
TR201806682T4 (tr)	2018-06-21	Farmasötik kombinasyonlar.
AU2006255559B2 (en)	2009-12-17	Combination of pyrimidylaminobenzamide compounds and imatinib for treating or preventing proliferative diseases
HK1062266B (en)	2010-02-26	Combination comprising a signal transduction inhibitor and an epothilone derivative
CZ20032277A3 (cs)	2004-01-14	Kombinace inhibitoru přenosu signálu a derivátu epothilonu k léčení proliferativních onemocnění
AU2011202950B2 (en)	2012-03-22	Use of c-Src inhibitors in combination with a pyrimidylaminobenzamide compound for the treatment of leukemia
AU2013201915A1 (en)	2013-04-11	Use of c-Src inhibitors in combination with a pyrimidylaminobenzamide compound for the treatment of leukemia
JP2010150238A (ja)	2010-07-08	悪性末梢神経鞘腫瘍の処置